In view of the important role of angiotensin converting enzyme in the renin-angiotensin system and therefore in the overall control of blood pressure it is important to pursue the chemical purification and characterization of converting enzyme and its relationship to bradykininase activity, and to identify the conditions which alter or control these enzyme activities. We will further purify human lung angiotensin I converting enzyme, particularly with regard to its chemical composition, kinetics and structure. We will also further purify converting enzyme obtained from human red cells and other human tissues (kidney, heart, liver, adrenals, and brain). Studies with possible converting enzyme inhibitors, particularly polypeptides and antihypertensive drugs will also be carried out. Purification of tissue extracts will be accomplished using standard ion exchange and gel filtration chromatography techniques as well as isoelectric focusing and disc gel electrophoresis. Lipid, carbohydrate, and amino acid composition and kinetic studies will be carried out by standard methods. Subunit structure will be examined by modifying extraction procedures and by treatment of purified enzyme with detergents, urea, heat, etc. Studies of converting enzyme activity in human and primate endothelial cell culture systems will be carried out, particularly endothelial cells derived from human and primate pulmonary artery, renal artery, umbilical vein, and femoral artery. The relationship of human lung bradykininase activity to human lung converting enzyme will be examined with particular emphasis on the mechanisms where by each of these systems is activated and controlled. These studies will contribute to better understanding of humoral cardiovascular control mechanisms, and the relationship of vasopressor and depressor systems, and may allow for the future development of inhibitors of potential therapeutic value.